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This month's issue features polyamines in milk, dairy’s association with improved short-term memory, reducing methane emission from livestock, and how lactation changes mammary fat cells. GutCheck:PolyaminesinHumanMilkAreEssentialforIntestinalMaturation
• Polyaminesareaminoacid-derivedmoleculesfoundinalllivingcellsandthemilkofallmammals,includinghumans.• Humanmilkpolyamineconcentrationishighestduringthefirstweeksoflactationandvariesacrossmothers.• Milkpolyaminesareessentialforoptimalmaturationoftheneonatalgut.
Putrescine,spermine,andspermidinemaynothavethemostappetizingnames,buttheseaminoacid-derivedmolecules(calledpolyamines)areingredientsofallmammalmilks.Thepresenceofpolyaminesinmilkisnotsurprising—putrescine,spermine,andspermidinearemanufacturedbyallmammalianbodycells,includingmammarytissue.Butpolyaminesarenotaccidentalmilkingredients,passedonsimplybecausetheyareubiquitousinmammaliancells.Researchfromhumanandnon-humananimalmodelsdemonstratesthatoptimalnutrientabsorption,thecompositionoftheintestinalmicrobiome,andevenfoodallergymayalldependonasufficientsupplyofpolyaminesduringtheneonatalperiod[1–11].Milkpolyamines,althoughoddinname,areessentialforthepropermaturationofthegastrointestinaltractinhumansandothermammals.
MakingPolyamines
Aminoacids,thebuildingblocksofproteins,arecomprisedofacarboxylgroupandanaminegroup.Polyamines,asthenamesuggests,arecomposedoftwoormoreaminegroups.Alllivingcellssynthesizepolyamines,andmammaliancellsmakethree—putrescine,spermidine,andspermine—byremovingthecarboxylgroupsfromtheaminoacidsmethionineandornithine[1].
Inmammals,polyaminesareinvolvedinnumerousfunctionswithincells:theyinfluencecellulargrowth,cellulardifferentiation,andthefunctionofcellmembranes,andalsoplayaroleinproteinsynthesisbyregulatingDNAandmessengerRNA[1,2].Althoughallcellsinamammal’sbodycansynthesizepolyamines,
theimportanceofasufficientdietarysupplytomaintainessentialphysiologicalfunctionsindicatesthatcellularpolyaminerequirementsexceedthebody’smanufacturingcapabilities[5,7].Inthissense,polyaminesareconsideredessentialnutrients,justlikecertainaminoacids,vitamins,andfattyacids[8].Thebody’spolyaminerequirementsvaryovertimeandareattheirhighestduringgrowthperiods,likeinfancy,whichischaracterizedbyrapidandwidespreadcellularproliferation[2].Thus,theinfancyperiodisatimewhenasufficientdietarysupplyofpolyaminesmaybeespeciallycritical.Polyaminesarepresentinallmammalianmilks,andalthoughtheconcentrationvariesacrossspecies(e.g.,humanmilkhashighervaluesthancowmilk),allmilkspeakinpolyamineconcentrationduringearlylactation[1,2].Forexample,inhumanmilk,polyaminesincreaseinconcentrationduringthefirsttwoweeksoflactation,reachtheirmaximumvalueduringthefirstmonth,andthendecrease[1].Thesechangesinconcentrationarebelievedtobeduetotheactionofthelactationhormoneprolactin,whichaugmentsmammaryglandsynthesisofpolyamines[2,8].Thatmilkfromcows,rats,pigs,andhumansallpeakinpolyamineconcentrationatthesamestageoflactationindicatesanimportantfunctionalroleforthesemoleculesduringthisperiod.Butifitweresimplyaboutgrowth(makingnewcells),polyamineswouldbeimportantthroughoutlactation.Whyarepolyaminessoimportantfornewbornmammals?
AGutFeeling
Mammalsvaryindevelopmentalmaturityatbirth;somearebornaltricialrequiringsignificantparentalinvestment,whereasothersaremoredevelopmentallymature,orprecocial.Onethingtheyallhaveincommon,however,istheconsumptionofmilkasafirstfood.Duringtheneonatalperiod,themammaliangastrointestinaltractundergoesrapidmaturationinpreparationfortheintroductionofnon-milkfoods.Polyamineingestionfrommilkisbelievedtohaveanessentialroleinthisaccelerateddevelopment
SPLASH!® milkscienceupdateMay2017Issue
ofthesmallandlargeintestines.Tounderstandandidentifyspecificfunctionsofpolyaminesinmammalianinfants,scientistsperformedexperimentsonnon-humananimalsthatincludedstudygroupsthatdidnotreceiveanypolyamines—whatbetterwaytofigureoutwhatsomethingdoesthantoobservewhathappenswhenyoutakeitaway.Theearlieststudies(duringthe1990s)focusedonratmodelsandfoundthatratpupsreceivingformulasupplementedwithpolyamines(specificallyspermineandspermidine)hadseveralphysiologicaldifferencesrelatingtogutmaturationcomparedwithcontrolsthatconsumedfewerornopolyamines.Keydifferencesincludedheightenedenzymaticactivityofthegut(includingenzymesresponsibleforproteindigestion)anddecreasedgutpermeabilitytomacromolecules[reviewedin5].Takentogether,theseobservationsledDandrifosseandcolleagues[5]toproposethatpolyaminesplayaroleinthedevelopmentoffoodallergy.Becausefoodproteinsarethesourceoffoodallergies,improvedproteindigestion(viaincreasedprotein-digestingenzymeactivity)coupledwithalesspermeablegut,reducesthepotentialforfoodantigenstomaketheirwayintothebloodstreamandtocomeincontactwiththeimmunesystem.Infantswithmorepermeablegutsduetoreducedpolyamineintake(particularlyspermine)wouldthusbeatahigherriskfordevelopingfoodallergies[5].Dandrifosseandcolleaguestestedtheirhypothesisinasmallsample(n=45)ofhumansubjects.First,milksampleswerecollectedfrommothersandanalyzedforpolyamineconcentration.Fiveyearslater,allmotherswerecontactedandsentaquestionnairerequestinginformationaboutenvironmentalandfoodallergiesintheirchild.Theyfoundthatbreastfedchildrenwithanallergyatage5consumedmilkwithlowerpolyamineconcentrationthanthosewithoutallergies.Theyevenestablishedwhattheybelievedwasa“criticalvalue”belowwhichchildrenhaveanincreasedriskofallergy(5.02nmol/ml)[5].Researchershavelonggrappledwiththequestionofwhetherbreastfeedingisprotectiveagainstallergy.Whereasseveralstudieshavefounddecreasedriskassociatedwithbreastfeeding,manyhavefoundtheriskfactorsareidenticalbetweentheformula-andbreastfedinfants.Thisstudy[5]helpstomakesenseofthosecontradictoryfindingsbyhighlightingthedifferencesinriskassociatedwithbreastfeedingalone.Somemothersproducemilkwithrelativelyhighconcentrationsofspermineandspermidinewithlittletonoriskofproducingallergy,whereasothersproducemilkwithlowerconcentrationsmoresimilartothosefoundinformula,whichhasaprobabilityofproducingafoodallergythatisbelievedtobecloserto80%[2,5].Infantformulaismadefromsoyorcowmilk,whichcanexplainthelowerconcentrationofpolyaminescomparedwithbreastmilk[9].Butwhatcanexplainthevariationinbreastmilkpolyamineconcentrationamonghumanmothers?Severallinesofevidencesuggestthatthepolyaminecompositionofthematernaldietinfluencesmilkpolyamineconcentration.Citrusfruits,suchasorangesandgrapefruitarehighinputrescine,whereasbeansandmeataregoodsourcesofspermineandspermidine[8].However,polyaminesarefoundinsomanydifferenttypesoffoodsthatitisdifficulttodetermineaparticulardietarypatternthatmayresultinhigherpolyamineintake.Gómez-Gallagoetal.[4]foundsignificantdifferencesintheconcentrationofmilkputrescineandspermidine(butnotspermine)acrossfourdifferenthumanpopulations(Finland,Spain,China,andSouthAfrica),whichtheyattributedtodietarydifferencesacrosscultures.AtiyaAlietal.demonstratedthisrelationshipwithamoredetailedstudy[7],whereinbreastfeedingmothersofnewbornskepta3-dayfooddiary.Aftercalculatingdailyintakeofallthreepolyamines,theyfoundthattheconcentrationofputrescine,spermidine,andspermineinmilkwereallsignificantlyassociatedwiththeirconcentrationinthediet.Inanotherstudy,AtiyaAlietal.[8]foundthatobesemothersproducedsignificantlylowerlevels(14%)ofputrescineandspermidine(butagain,notspermine)comparedwithmotherswithahealthybodymassindex.Althoughobesityitselfcouldbeacontributingfactortomilkpolyaminelevels,theyobservedthatobesemothersthatreceivednutritionalcounselingandadviceduringthestudyperiodincreasedtheirmilkpolyaminelevelstothosematchinghealthycontrols.Thisfindingsuggestsitisnotwhatthemotherhaseateninthepast,butwhatthemotheriscurrentlyconsumingthatdeterminesmilkpolyamineconcentration.Except,perhaps,forspermine,theverypolyamineimplicatedingutpermeability.Allthreestudies[4,7,8]concludedthatspermineappearslesssusceptibletoenvironmentalinfluences.However,interpretationsofresultsarecomplicatedbythefactthatpolyaminescanbeinterconvertedbytheinfant(putrescineisaprecursortospermineandspermidine,andcanbebrokendowntomakeeitherpolyamine;spermineandspermidinecanalsobeconvertedbackintoputrescine).Thus,thetotalcontentofpolyaminesinmilkshouldbethemetricofinterest.
GrowingtheGut
Tworecentanimalstudieshaveprovidedmoredetailedevidenceofthepotentialhealthoutcomesassociatedwithlowmilkpolyamineconcentration[6,10].VanWettereetal.[10]wereinterestedintherelationshipbetweenmilkpolyaminesandthedevelopmentoftheabsorptive,ormucosal,surfaceoftheintestines(thatis,thesurfacewherethefoodmeetstheintestinalcells).Themucosalsurfaceoftheintestineslooksabitlikearollercoaster,withaseriesofpeaks(calledvilli)andvalleys(calledcrypts).Itisalongthissurfacethatnutrients(includingproteins,fats,carbohydrates,vitaminsandminerals)areabsorbedintotheintestinesforeventualtransferintothebloodstream.Thisrollercoaster-likestructureisaratheringeniouswayofgettingmoresurfaceareafornutrientabsorption;thehigherthepeaksandthedeeperthevalleys,themorecellsforfoodtocontactforabsorption.VanWettereetal.[10]foundthatpigletssupplementedwithspermineeveryotherdayovera10-dayperiodhadanincreaseinthesurfacearea
oftheirgastrointestinaltract.Andtheincreasewassignificant;sperminesupplementationwasassociatedwitha41%increaseinvillusheight(thepeaks)anda21%decreaseincryptdepth(thevalleys)alongthesmallintestine[10].Importantly,theinvestigatorswereabletolinkthechangesintheintestinalsurfaceareawithimprovedgrowthbothduringsupplementationandafterweaning[10].Higherhillsandlowervalleysmeantimprovednutrientabsorption,whichtheyarguewascriticalinhelpingthepigletsmaintainoptimalgrowthratesastheytransitionedfrommilktonon-milkfoods.Thesurfaceareaoftheintestinesisnottheonlythinginthegutthatmilkpolyamineshelptogrow—thesemoleculesarealsogrowthfactorsforthehealthybacteriathatpopulatethegastrointestinaltract.Inanewstudy,Gómez-Gallagoandcolleagues[6]foundthatnewbornmiceconsumingpolyamine-supplementedformulahadbacterialcommunitiessimilartothoseofmiceconsumingtheirmother’smilk,validatingtheirresultsfromapreviousstudy[11].Becauseofthestrongconnectionbetweenthedevelopmentofahealthygutmicrobiomeandimmunefunction,theirnewstudywentonestepfurtherandinvestigatedthetypesoflymphocytes(cellsoftheimmunesystem)thatpopulatedthegutaswellasgenesrelatedtoimmuneactivitywithinthegut.Again,micefedthesupplementedformulaweregroupedstatisticallyclosertothesucklingmicethanthoseconsumingformulawithoutpolyamines[6].Itisintriguingtothinkthathumaninfantswouldhaveidenticalresponsestopolyaminesupplementationasthepigletsandmousepupsintheexperimentalmodels.Optimalintakelevelsofpolyaminesforhumaninfantshavenotbeenestablished.However,bothstudies[6,10]foundsignificantresultsusingconcentrationsofpolyaminesthatwerelowerthanthoseinmouseorpigmilk,indicatingthathumanbreastmilkconcentrationscouldbeahelpfulsignpostfordetermininganappropriateconcentration.Couldsomethingassimpleaspolyaminesupplementationinformula(orincreasedpolyamineconsumptioninthedietofbreastfeedingmothers)helpresolvehealthissuesassociatedwithfoodallergy,nutrientabsorption,ortheintestinalmicrobiome?Gómez-Gallagoetal.[6]suggestthisquestionisimportantenoughtogo“onestepforward”byreproducingtheirexperimentsusinghumansubjects.
Löser,C.,2000.Polyaminesinhumanandanimalmilk.BritishJournalofNutrition,84(S1):55-58. Larqué,E.,Sabater-Molina,M.,Zamora,S.,2007.Biologicalsignificanceofdietarypolyamines.Nutrition,23(1):87-95. Plaza-Zamora,J.,Sabater-Molina,M.,Rodriguez-Palmero,M.,Rivero,M.,Bosch,V.,Nadal,J.M.,Zamora,S.,Larque,E.,2013.Polyaminesinhumanbreastmilkfor
pretermandterminfants.BritishJournalofNutrition,110(03):524-528. Gómez-GallegoC,KumarH,García-MantranaI,duToitE,SuomelaJP,LinderborgKM,ZhangY,IsolauriE,YangB,SalminenS,ColladoMC.,2017.Breastmilk
polyaminesandmicrobiotainteractions:Impactofmodeofdeliveryandgeographicallocation.AnnalsofNutritionandMetabolism,March17. Dandrifosse,G.,Peulen,O.,ElKhefif,N.,Deloyer,P.,Dandrifosse,A.C.Grandfils,C.,2000.Aremilkpolyaminespreventiveagentsagainstfoodallergy?.
ProceedingsoftheNutritionSociety,59(01):81-86. Gómez-GallegoC.,GarciaRomoM.,FriasR.,Periago,M.J.,Ros,G.,SalminenS.,ColladoM.C.,2017.Miceexposedtoinfantformulaenrichedwithpolyamines:
impactonhosttranscriptomeandmicrobiome.Food&Function. AtiyaAli,M.,Strandvik,B.,Sabel,K.G.,PalmeKilander,C.,Strömberg,R.Yngve,A.,2014.Polyaminelevelsinbreastmilkareassociatedwithmothers’dietary
intakeandarehigherinpretermthanfull-termhumanmilkandformulas.JournalofHumanNutritionandDietetics,27(5):459-467. AtiyaAli,M.,B.Strandvik,C.Palme-Kilander,A.Yngve.,2013.Lowerpolyaminelevelsinbreastmilkofobesemotherscomparedtomotherswithnormalbody
weight.JournalofHumanNutritionandDietetics26(s1):164-170. Buts,J.P.,DeKeyser,N.,DeRaedemaeker,L.,Collette,E.,&Sokal,E.M.,1995.Polyamineprofilesinhumanmilk,infantartificialformulas,andsemi-elemental
diets.Journalofpediatricgastroenterologyandnutrition,21(1):44-49. vanWettere,W.H.E.J.,Willson,N.L.,Pain,S.J.,Forder,R.E.A.,2016.Effectoforalpolyaminesupplementationpre-weaningonpigletgrowthandintestinalcharacteristics.animal(Oct1):.1-5.
Gómez-GallegoC.,Collado,M.C.,Perez,G.,Ilo,T.,Jaakkola,U.M.,Bernal,M.J.,Periago,M.J.,Frias,R.,Ros,G.,Salminen,S.,2014.Resemblingbreastmilk:influenceofpolyamine-supplementedformulaonneonatalBALB/cOlaHsdmousemicrobiota.BrJNutr111:1050-1058.
ContributedbyDr.LaurenMilliganNewmarkResearchAssociateSmithsonianInstitute
HighDairyConsumptionisAssociatedwithBetterShort-TermMemoryinMen• Anewstudyinvestigatestheeffectsofdairyintakeonshort-termmemory,usingmatchedpairsoftwinstoadjustfor
geneticandfamilyenvironmentalfactors.• Thestudyfoundthathigherdairyproductconsumptionwassignificantlyassociatedwithbettershort-termmemoryin
menbutnotwomen.• Short-termmemoryassessmentcanbeusedtoscreenformildcognitiveimpairmentandAlzheimer’sdisease,andthe
newstudythussuggeststhatdairyintakecouldpotentiallyreducecognitivedeclineinmenindependentofgeneticsandfamilyenvironment.
Eatingdairyproductspositivelyinfluencesbrainfunction,withhigherdairyintakeassociatedwithimprovedcognitiveabilityandshort-termmemory,andreducedcognitivedeclineanddementia[1-8].However,previousstudiesthatlookedattheseassociationscouldnotruleouttheeffectsofconfoundingfactorssuchasgeneticsandfamilyenvironment,whicharealsoknowntoaffectcognitiveabilityandfoodintake[9,10].
Onewaytoteaseaparttheeffectsofdairyfromthoseofgeneticsandfamilyenvironmentwouldbetostudypairsoftwins,andthat’sexactlytheapproachtakenbySoshiroOgataandhiscolleaguesatOsakaUniversityGraduateSchoolofMedicine.Inanewstudy,theresearchersinvestigatedtheassociationbetweendairyproductintakeandshort-termmemory,usingnaturallymatchedtwinpairstoadjustfornearlyallgeneticandfamilyenvironmentalfactors[11].
OgataandhiscolleaguescollecteddatafromtheOsakaUniversityCenterforTwinResearch,andanalyzed39Japanesemaletwinpairsand139Japanesefemaletwinpairs[11].Toassessshort-termmemory,theresearchersaskedparticipantstolistentotwoshortstoriesandimmediatelyrecallthedetails.Theresearchersassessedparticipants’dietsusingaself-administereddiethistoryquestionnaire,andtheparticipants’dairysourcesconsistedoflow-fatandfull-fatmilkandyogurt.Theresearchersfoundthathigherconsumptionofdairyproductswassignificantlyassociatedwithbettershort-termmemoryinmen,evenafteradjustingfornumerousconfoundingfactorsincludingalmostallgeneticandfamilyenvironmentalfactors.Theresearchersdidnotfindasimilarassociationinwomen.
Short-termmemoryassessmentcanbeusedtoscreenformildcognitiveimpairmentandAlzheimer’sdisease[13].TheresultsofOgataetal.[12]thussuggestthateatingmoredairyproductscouldpotentiallyreducecognitivedeclineinmenindependentofgeneticsandfamilyenvironment.It’sunclearfromthisstudywhyhigherdairyintakewasassociatedwithbettershort-termmemoryinmenandnotinwomen.Theresultsareconsistentwithapreviouslongitudinalstudythatfoundnosignificantassociationbetweencognitivefunctionandconsumptionofdairyproductsinwomen[14].Theresearchersalsosuggestthatthesexdifferencesintheeffectsofdairyonshort-termmemorymightbeduetodifferencesintheagedistributionofmenandwomeninthestudy,orduetopreviouslydescribedseasonalvariationsindairyconsumptioninJapanesewomenbutnotmen[15].Futurestudiesareneededtoelucidateboththereasonsfortheobservedsexdifferencesandthemechanismsbywhichdairyconsumptionaffectscognitivefunction.Onepotentialmechanisminvolvestheeffectsofincreaseddairyproductconsumptiononareducedriskofdevelopingtype2diabetesandhypertension,whicharepotentialriskfactorsforcognitivedecline[16-18].DairyalsocontainsnutritionalcomponentssuchascalciumandvitaminB12thatareknowntohavesomecognitiveeffects.Theauthorssuggestthatfollow-upstudiescouldmeasuretheeffectsofdairyonothercognitiveabilitiesinadditiontoshort-termmemory.Thesestudiescouldalsoinvestigatedifferencesbetweentheeffectsoffull-fatandlow-fatdairyproductsoncognitivefunction,aspreviousstudiesindicateddifferencesintheireffects[19,20].Byshowingthatdairymayinfluenceshort-termmemoryregardlessofgeneticandenvironmentalfactors,thecurrentstudyindicatesthatlookingmoredeeplyattheeffectsofdairyoncognitionisano-brainer.
Gomez-PinillaF.Brainfoods:theeffectsofnutrientsonbrainfunction.NatRevNeurosci.2008Jul;9(7):568-78. EverittA.V.,HilmerS.N.,Brand-MillerJ.C.,JamiesonH.A.,TruswellA.S.,SharmaA.P.,MasonR.S.,MorrisB.J.,LeCouteurD.G.Dietaryapproachesthatdelayage-
relateddiseases.ClinIntervAging.2006;1(1):11-31. CamfieldD.A.,OwenL.,ScholeyA.B.,PipingasA.,StoughC.Dairyconstituentsandneurocognitivehealthinaging.BrJNutr.2011Jul;106(2):159-74. RahmanA.,SawyerBakerP.,AllmanR.M.,ZamriniE.Dietaryfactorsandcognitiveimpairmentincommunity-dwellingelderly.JNutrHealthAging.2007Jan-
Feb;11(1):49-54. ParkK.M.,FulgoniV.L.TheassociationbetweendairyproductconsumptionandcognitivefunctionintheNationalHealthandNutritionExaminationSurvey.BrJ
Nutr.2013Mar28;109(6):1135-42. CrichtonG.E.,EliasM.F.,DoreG.A.,RobbinsM.A.Relationbetweendairyfoodintakeandcognitivefunction:theMaine-SyracuselongitudinalStudy.IntDairyJ.
2012Jan1;22(1):15-23. YamadaM.,KasagiF.,SasakiH.,MasunariN.,MimoriY.,SuzukiG.Associationbetweendementiaandmidliferiskfactors:theradiationeffectsresearch
foundationadulthealthstudy.JAmGeriatrSoc.2003Mar;51(3):410-4. OzawaM.,OharaT.,NinomiyaT.,HataJ.,YoshidaD.,MukaiN.,NagataM.,UchidaK.,ShirotaT.,KitazonoT.,KiyoharaY.Milkanddairyconsumptionandriskof
dementiainanelderlyJapanesepopulation:theHisayamaStudy.JAmGeriatrSoc.2014Jul;62(7):1224-30. LeeT.,HenryJ.D.,TrollorJ.N.,SachdevP.S.Geneticinfluencesoncognitivefunctionsintheelderly:aselectivereviewoftwinstudies.BrainResRev.2010
Sep;64(1):1-13 HasselbalchA.L.,HeitmannB.L.,KyvikK.O.,SørensenT.I.Studiesoftwinsindicatethatgeneticsinfluencedietaryintake.JNutr.2008Dec;138(12):2406-12. OgataS.,TanakaH.,OmuraK.,HondaC.;OsakaTwinResearchGroup,HayakawaK.Associationbetweenintakeofdairyproductsandshort-termmemorywithandwithoutadjustmentforgeneticandfamilyenvironmentalfactors:Atwinstudy.ClinNutr.2016Apr;35(2):507-13.
HayakawaK.,IwataniY.AnoverviewofmultidisciplinaryresearchresourcesattheOsakaUniversityCenterforTwinResearch.TwinResHumGenet.2013Feb;16(1):217-20.
RabinL.A.,PareN.,SaykinA.J.,BrownM.J.,WishartH.A.,FlashmanL.A.,SantulliR.B.DifferentialmemorytestsensitivityfordiagnosingamnesticmildcognitiveimpairmentandpredictingconversiontoAlzheimer’sdisease.NeuropsycholDevCognBAgingNeuropsycholCogn.2009May;16(3):357-76.
VercambreM.N.,Boutron-RuaultM.C.,RitchieK.,Clavel-ChapelonF.,BerrC.Long-termassociationoffoodandnutrientintakeswithcognitiveandfunctionaldecline:a13-yearfollow-upstudyofelderlyFrenchwomen.BrJNutr.2009Aug;102(3):419-27.
SasakiS.,TakahashiT.,IitoiY.,IwaseY.,KobayashiM.,IshiharaJ.,AkabaneM.,Tsugane,S.;JPHC.Foodandnutrientintakesassessedwithdietaryrecordsforthevalidationstudyofaself-administeredfoodfrequencyquestionnaireinJPHCStudyCohortI.JEpidemiol.2003Jan;13(1Suppl):S23-50.
Soedamah-MuthuS.S.,VerberneL.D.M.,DingE.L.,EngberinkM.F.,GeleijnseJ.M.Dairyconsumptionandincidenceofhypertension:adose-responsemeta-analysisofprospectivecohortstudies.Hypertension.2012Nov;60(5):1131-7.
MonetteM.C.E.,BairdA.,JacksonD.L.Ameta-analysisofcognitivefunctioninginnondementedadultswithtype2diabetesmellitus.CanJDiabetes.2014Dec;38(6):401-8.
GiffordK.A.,BadaraccoM.,LiuD.,TripodisY.,GentileA.,LuZ.,PalmisanoJ.,JeffersonA.L.Bloodpressureandcognitionamongolderadults:ameta-analysis.ArchClinNeuropsychol.2013Nov;28(7):649-64.
CrichtonG.E.,MurphyK.J.,BryanJ.Dairyintakeandcognitivehealthinmiddle-agedSouthAustralians.AsiaPacJClinNutr.2010;19(2):161-71. AlmeidaO.P.,NormanP.,HankeyG.,JamrozikK.,FlickerL.Successfulmentalhealthaging:resultsfromalongitudinalstudyofolderAustralianmen.AmJGeriatrPsychiatry.2006Jan;14(1):27-35.
ContributedbyDr.SandeepRavindranFreelanceScienceWriterSandeepr.comLesseningtheGasLeak
• Methaneemissionsfromlivestock—intheformofbelchesandflatulence—composeanon-negligibleproportionofgreenhousegasemissions.
• Inanexperiment,theadditionofthemethaneinhibitor,3-nitrooxypropanol(3NOP),toanimalfeedcutdairycattle’smethaneemissionsbyabout30%,withoutaffectingtheanimals’productivity.
• Crucially,theexperimentwasconductedoveraprolongedperiodundersimilarconditionstohowdairycattlearenormallykeptonNorthAmericancommercialfarms.
Ateamofscientistsfromfourcontinentshasgatheredevidencetodemonstratethatitshouldbepossibletocutmethaneemissionsfromdairycattlewithoutreducinghowmuchmilktheyproducenorhavingtochangetheconditionsinwhichtheyarekept.Theanswerissimplytoaddaningredienttotheirfeed.Intestslastingseveralmonths,thisingredient,3-nitrooxypropanol,knownas3NOP,cutmethaneemissionsfromHolsteindairycowsbyabout30%[1].Achievingsuchareductioninentericmethaneoutputacrossthedairyindustrywouldbeasignificantcontributiontowidereffortstoreducegreenhousegasemissions.
Asruminants,dairycattlearehometobacteriathatfermenttheirfood,readyingitforregurgitationascudbeforeproperdigestiontakesplace.Methanegasisgeneratedduringthefermentationprocessandeventuallymakesitswayintotheatmospherefromeitheroneendofthecowortheother.Allofthismethane—emanatingfromcattleallovertheworld—isaprimetargetformitigatinggreenhousegasemissions,notleastbecausemethaneisafarmorepotentgreenhousegasthancarbondioxide.Althoughestimatesoflivestock’scontributiontoanthropogenicemissionsvary[2],itiswidelyacceptedthatemissionsfromcattledwarfthosefromotherkindsoflivestock[3].Theauthorsoftherecentstudysetouttoevaluatethereal-worldeffectivenessofacompoundthattheyknewhadthepotentialtocuthow
muchmethanetheaveragedairycowreleasesintotheatmosphere.3NOPwasfirstidentifiedbyacomputermodelinalaboratoryinBasel,Switzerland.Researcherstheresingleditoutforfurthertestingbecauseafteritwasfoundtobindtheactivesiteofamethane-producingenzymethatoccursinoneofthemostcommonkindsofruminantfermentationbacteria,Methanobrevibacterruminantium.Bybindingthisactivesite,3NOPstopstheenzymefromworkingandlimitsthebacterium’sgrowth(whilstleavingunaffectedthegrowthofnon-methane-producingbacteria)[4].Testingthereal-worldeffectivenessrequired48Holsteins.Thecowswererandomlyassignedtoeitheracontrolgroup,ortoagroupthatwouldcontinuallyreceivelow,medium,orhighamountsof3NOPinitsfood.Manyaspectsofthecows’milkproductionandhealthwerecloselymonitored,andalloftheirmethane,carbondioxideandhydrogenemissionsweremeasuredregularlythroughouttheexperiment.Importantly,theHolsteinswerekeptinconditionssimilartothoseoncommercialdairyfarmsandmonitoredforathreefullmonths—whichislongerthanmostmethane-inhibitortestsofthepast.Theextendedperiodoffersaninsightintowhetherseveralkeyconcernsareavoided,suchasifthecowseatlessovertimeintheconditionwherethecompoundisaddedtotheirfood;iftheirmilkproductiontailstailedoff;andifmethane-producingbacteriacanshifttheirmetabolicstrategyandadaptto3NOP.Ifthelatteroccurs,methaneproductionmaystarttoriseagainafteritdips—despitethecowscontinuingtogobble3NOPineverymeal.Afterthethreemonthswereup,theHolsteinsthatatethemost3NOPconsistentlyemittedtheleastmethane.Indeed,theygenerated32%lessmethanethancowsinthecontrolgroup,whichconsumedno3NOPbutanotherwiseidenticaldiet.Thetrendinthedatashowedlittlesignofabating,indicatingthatmethane-generatingbacteriadonotreadilyfindawayaroundthemethaneinhibitor’seffects.The3NOP-consumingcowsproducedmorehydrogen,whichwastobeexpectedifthefermentationprocesswas
interruptedasthescientistsforesaw(becausehydrogenisanintermediateinthisprocess).Carbondioxideemissionsdidnotvary,however,whateverexperimentalgroupthecowswerein.Thecows’othervitalstatisticswereencouraging.Eating3NOPdidnotcurbtheirappetites;instead,itseemstohavehelpedthemputonweight.Thisisprobablybecausethefoodenergynormallylostasmethanebecamemetabolicallyavailabletotheseanimals.Additionalenergyavailabilitymayalsoexplainthegreatermilkproteinandlactoseyieldsinthe3NOP-eatingcows’milk,sinceitcould,inpart,havebeenplowedintosynthesizingthesemilkconstituents.Overall,theconcentrationoffatinmilkwasunaffectedbyadietcontaining3NOP(eventhoughtherelativeabundancesofparticularfatsdidchange).Whilefurthertestingislikelyrequiredonlargerherdsanddifferentbreeds,3NOPdoesappeartogeneratethekindofmethanemitigationthatthedairyindustryisunderpressuretoachieve,withoutimpactinghowfarmersgoabouttheirbusiness.Thismattersinmanycountrieswheretheindustrycontributesasizeableportionoftotalgreenhousegasemissions,suchasNewZealand.ButitalsocomesatanauspicioustimeintheUnitedStatesbecausetheU.S.EnvironmentalProtectionAgency’sestimatesforentericmethaneemissionsoverthecountryhave,inthepastfewyears,comeunderfire.SatellitedatahavesuggestedthattheAgencyunderestimatestheseemissionsbyupto85%[2].3NOPcouldhelptoreducetheproblem.
HristovaA.N.,OhaJ.,GiallongoaF.,FrederickaT.W.,HarperaM.,WeeksaH.L.,BrancobA.F.,MoatecP.J.,DeightoncM.H.,WilliamscS.R.O.,KindermanndM.,DuvaleS.(2015)Aninhibitorpersistentlydecreasedentericmethaneemissionfromdairycowswithnonegativeeffectonmilkproduction.PNAS,112(34):10663–10668.
WechtK.J.,JacobD.J.,FrankenbergC.,JiangZ.,BlakeD.R.(2014)MappingofNorthAmericanmethaneemissionswithhighspatialresolutionbyinversionofSCIAMACHYsatellitedata.JGeophysResAtmos119(12):7741–7756.
HerreroM.,HendersonM.,HavlíkP.,ThorntonP.K.,ConantR.T.,SmithP.,WirseniusS.,HristovA.N.,GerberP.,GillM.,Butterbach-BahlK.,ValinH.,GarnettT.&StehfestE.(2016)Greenhousegasmitigationpotentialsinthelivestocksector.NatureClimateChange6:452-461.
DuinE.C.,WagnerT.,ShimaS.,PrakashD.,CroninB.,Yáñez-RuizD.R.,DuvalS.,RümbeliR.,StemmlerR.T.,ThauerR.K.,KindermannM.(2016)Modeofactionuncoveredforthespecificreductionofmethaneemissionsfromruminantsbythesmallmolecule3-nitrooxypropanol.PNAS113(22):6172-7.
ContributedbyAnnaPetherickProfessionalsciencewriter&editorwww.annapetherick.com
TheManyLivesofFatCells• Thereareatleastthreetypesoffatcells,eachwithdifferentfunctions.• Substantialchangesinmammaryfatcellsoccurduringthelactationcycle.• Somemilkproducingcellsinmammarytissuebecomebrown-likefatcellswhenmilkisnolongerproduced.
Peopleobsessaboutfat.Manyhavemuchmorefatthantheyneeddepositedinvariouslocationsinthebodyanditthreatensbothhealthandfashion.Fathasnowdevelopedabadreputation.Intimesgoneby,abitofextrafatmeantalifesavingenergyreserveintimesoffoodscarcity.Indeed,themetabolismwehaveinheritedfromourancestorswasoriginallyfine-tunedtosuitthefeastorfaminelifestyleofthepast;however,itisnotsuitableformostpeopleintoday’sworldwherefoodabundanceisthenorm.Fatisasimplething,orsowethought.Therehavebeenseveralsurprisesoflate.
FatTissuesAreNotAllTheSame
Thebodyofamammalcontainsdifferenttypesoffat,eachwithspecificfunctions.Scientistshavelongknownthatthemainfunctionsoffatinanimalsarethestorageofenergyintheformofspecificfattyacidscalledtriglyceridesandtheprotectionofinternalorgansfrombluntforcetrauma.Thefattypethatlargelycharacterizesthesefunctionsiswhitefat(adipose)tissue,whichisprimarilymadeoffatcellscalledwhiteadipocytesthatarerelativelylarge,andasinglelargeglobuleoffattypicallydominatestheirinternalstructure.Thisisthefatweallknowsowell.Asecondtypeoffat,brownadiposetissue,wasfirstdiscoveredinhibernatingmammals,likebears.Unlikewhiteadiposetissue,brownadiposetissuehastheuniquepropertyofheatgeneration,whichallowshibernatinganimalstowithstandseverecold.Thisadiposetissueconsistsofbrown
adipocyteswitheachcontainingmanysmallfatglobulesandalargenumberofmitochondria,thepowerhousesofacell.Thelattergivethistissueitsbrowncolor,andaspecificbiochemicalreactioninthemgeneratesheat.Newbornoffspringofnon-hibernatingmammals,includinghumans,alsocontainbrownadiposetissuethatprotectsthemfromthecoldwhentheyareattheirmost
vulnerable.Withinafewweeksofbirth,however,thebrownadiposetissueinmostnewbornmammalsislostandreplacedbywhiteadiposetissue[1].Oneofthescientificsurprisesdiscoveredoverthelastdecadeisthatadulthumanshaveasmallamountofbrownadiposetissueintheneckandshoulderregion(interscapularregion)closetothemajorbloodvesselsleadingtothebrain.Presumably,theprimaryfunctionofthisadiposetissueistoheatbloodflowingtothebrainwhenthebodyisexposedtoverycoldtemperatures.Thisadiposetissuemayalsohavearoleinregulatingmetabolism[1–3].Anothersurprisemadeonlyoverthelastfewyearswasthediscoverybyscientistsofathirdtypeoffatthatconsistsofbrown-likeadipocytesinducedbydietorcoldwithinwhiteadiposetissue[2,3].Researcherscallthistypeoffatbeigeadiposetissue.Eventhoughbeigeadipocyteslooklikebrownadipocytes,theyaredifferentintermsoftheircellularoriginandfunction.Scientistsfromseveralgroupshaveconcludedthatbeigeadiposetissuemighthelpprotectpeoplefromobesitybyincreasingtherateofmetabolismoffattyacids[3].Consequently,manyscientificgroupsinboththepublicdomainandprivatecompaniesareinvestigatingdietaryanddrug-basedstrategiesthatmayincreasetheamountofbeigeadiposetissueinobesepeople[3,4].
TheLactationCycleCausesSubstantialChangesinMammaryFatCells
AscientificgroupledbySaverioCintithatinvolvedresearchersfromsixuniversitiesandthreecontinentsrecentlyconcludedthatadipocytespresentinmammarytissueundergoadramaticchangeduringthelactationcycle[5].Thisisthecycleofmilkproductionandcessationoccurringinmammarytissuebetweenonepregnancyandthenext.Duringlactation,mammaryepithelialcellssecretethevariouscomponentsofmilkintomammarytissuealveoli(smallsacsfoundwithinthemammarygland).Whenthereisnolongeranysucklingbytheyoungandremovalofmilkfrommammarytissue,thetissueundergoesadramaticcellularrestructuringcalledinvolutionthatstopsmilkproduction.Somemammaryepithelialcellsdiebutmostreverttoaquietstatenolongerproducingmilk.Theresearchersusedtheremarkablegenetictoolsavailableforstudyingtransgenicmicetovisualizethefateoffatcellslyingadjacenttothemammaryepithelialcellsduringthelactationcycle.Theyusedlightmicroscopyandtheamazingpoweroftransmissionelectronmicroscopytoproduceexquisiteimagesoftheseadiposecellsduringandafterlactation.Thescientists’approachalloweddeterminationoftheadipocytetypeinmammarytissuethroughoutthelactationcycle.Cinti[1]showedthatduringpregnancyandlactationsomewhiteadipocytesinthemammaryglandconvertedintomilk-secretingepitheliacells,quitearemarkablecellulartransformation.Thiswasalreadyknown[6].Thesurprisewasthatwhentheyexaminedmammarytissueduringtheprocessofinvolutiontheyfoundthatsomemilksecretingepithelialcellschangedintobrown-likeadipocytes,aprocesscalledtransdifferentiation,wherebyacellofonedistincttypeconvertsintoanothertype.Itisstillunclearwhetherthesecellsarebrownorbeigeadipocytes.However,whiteandbeigeadipocytesoriginatefromthesamecellprecursorssuggestingthatthesemammaryadipocytesininvolutingmammarytissuecouldbebeigeadipocytesratherthanbrownadipocytes.Thelactationcyclethereforehighlightsthestrikingfunctionalplasticityofadipocytesinmammarytissue.Theinvestigatorsdidnotcommentonthefunctionsofthebrown-likeadipocytesininvolutingmammarytissue.Clearly,thestudyisanotherexamplehighlightingthemanylivesoffatcellsandtheirunderappreciatedimportanceindiversebiologicalfunctions.
Cinti,S.Theadiposeorganataglance.DisModelMech5,588-594(2012). Giralt,M.&Villarroya,F.White,brown,beige/brite:differentadiposecellsfordifferentfunctions?Endocrinology154,2992-3000(2013). McMillan,A.C.&White,M.D.Inductionofthermogenesisinbrownandbeigeadiposetissues:molecularmarkers,mildcoldexposureandnoveltherapies.Curr
OpinEndocrinolDiabetesObes22,347-352(2015). Kim,S.H.&Plutzky,J.Brownfatandbrowningforthetreatmentofobesityandrelatedmetabolicdisorders.DiabetesMetabJ40,12-21(2016). Giordano,A.etal.Mammaryalveolarepithelialcellsconverttobrownadipocytesinpost-lactatingmice.JCellPhysiolFebruary14edition(2017). Morroni,M.etal.Reversibletransdifferentiationofsecretoryepithelialcellsintoadipocytesinthemammarygland.ProcNatlAcadSciUSA101,16801-16806
(2004).ContributedbyDr.RossTellam(AM)ResearchScientistBrisbane,Australia
EditorialStaffofSPLASH!milkscienceupdate:Dr.DanielleLemay,ExecutiveEditorDr.KatieRodger,ManagingEditorAnnaPetherick,AssociateEditorProf.KatieHinde,ContributingEditorDr.LaurenMilliganNewmark,AssociateEditorDr.RossTellam,AssociateEditorDr.SandeepRavindran,AssociateEditorProf.PeterWilliamson,AssociateEditorCoraMorgan,EditorialAssistantTasslynGester,CopyEditor
FundingprovidedbyCaliforniaDairyResearchFoundationandtheInternationalMilkGenomicsConsortium
TheviewsandopinionsexpressedinthisnewsletterarethoseofthecontributingauthorsandeditorsanddonotnecessarilyrepresenttheviewsoftheiremployersorIMGCsponsors.
